Twice-daily Trizivir versus Combivir-abacavir in antiretroviral-experienced adults with human immunodeficiency virus-1 infection: a formulation-switch trial.

Abstract

STUDY OBJECTIVE:

To establish the clinical equivalence (noninferiority) of one tablet containing abacavir 300 mg-lamivudine 150 mg-zidovudine 300 mg (Trizivir) versus a tablet containing lamivudine 150 mg-zidovudine 300 mg (Combivir) given with one abacavir (ABC) 300-mg tablet, administered twice/day, in antiretroviral-experienced, human immunodeficiency virus (HIV)-1-infected patients.

DESIGN:

Randomized, open-label, parallel-group, multicenter, formulation-switch study.

SETTING:

Twenty seven outpatient treatment sites.

PATIENTS:

Adults with HIV-1 RNA levels of 400 copies/ml or less and CD4+ cell counts above 200 cells/mm3 who had been treated for 16 weeks or more with highly active antiretroviral therapy containing Combivir-ABC.

INTERVENTION:

Patients were randomized 1:1 to Trizivir (97 patients) or Combivir-ABC (98) for 24 weeks.

MEASUREMENTS AND MAIN RESULTS:

The primary study end point was the proportion of patients who maintained less than a 0.5-log10 increase from baseline in HIV-1 RNA (virologic success) through week 24. Clinical equivalence of the treatments was established if the 95.1% lower confidence limit (LCL) for the difference in proportion of virologic success with Trizivir minus Combivir-ABC was -0.12 or greater. Trizivir was clinically equivalent to Combivir-ABC. The intent-to-treat observed analysis at week 24 with Trizivir and Combivir-ABC showed a similar rate of virologic success (83% [80/97] and 77% [75/98], respectively, 95.1% LCL -0.026), of patients with HIV-1 RNA levels of 400 or fewer copies/ml (99% [82/83] and 93% [77/83], respectively, 95.1% LCL 0.021), and of patients with HIV-1 RNA levels of fewer than 50 copies/ml (89% [74/83] and 77% [64/83], respectively, 95.1% LCL 0.038). The intent-to-treat missing = failure analysis showed comparable results. Changes in CD4+ cell count from baseline, overall mean self-reported adherence (Trizivir 97%, Combivir-ABC 92%), and adverse events did not differ significantly between treatments. No ABC-related hypersensitivity reactions occurred.

CONCLUSION:

Trizivir was clinically equivalent to Combivir-ABC and may be substituted for the latter to simplify treatment and reduce pill burden.

• Authors: Margaret A Fischl, Alfred E Burnside Jr, Charles E Farthing, Melanie A Thompson, Nicholaos C Bellos, Vanessa C Williams, Teresa L Kauf, Paul G Wannamaker, Mark S Shaefer, ESS40005 Study Team
• Journal: Pharmacotherapy (Pharmacotherapy) Vol. 23 Issue 11 Pg. 1432-40 (Nov 2003) ISSN: 0277-0008 [Print] United States
• PMID: 14620390 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Dideoxynucleosides
• Drug Combinations
• RNA, Viral
• abacavir, lamivudine, and zidovudine drug combination
• lamivudine, zidovudine drug combination
• Lamivudine
• Zidovudine
• abacavir

Topics

• Adolescent
• Adult
• Analysis of Variance
• Anti-HIV Agents (administration & dosage)
• Chemistry, Pharmaceutical
• Confidence Intervals
• Dideoxynucleosides (administration & dosage)
• Drug Administration Schedule
• Drug Combinations
• Female
• HIV Infections (blood, drug therapy)
• HIV-1 (drug effects, metabolism)
• Humans
• Lamivudine (administration & dosage)
• Male
• Middle Aged
• RNA, Viral (blood)
• Zidovudine (administration & dosage)